Trodelvy (sacituzumab govitecan-hziy)

In contrast, TROP2-directed ADCs demonstrate negligible cardiac signals. Given the elevated fatality rate of serious cardiac events associated with T-DXd observed in real-world data, we propose a risk-stratified cardiac monitoring algorithm incorporating high-sensitivity troponin and global longitudinal strain for patients receiving next-generation ADCs.

While TROP2-targeted antibody-drug conjugates (ADCs), such as sacituzumab govitecan, sacituzumab tirumotecan, and datopotamab deruxtecan (DXD), achieved clinical success, the mechanisms underlying resistance to these therapies remain incompletely understood. R7059-DXD is a differentiated, epitope-distinct TROP2-targeted ADC with the potential to overcome resistance to existing therapies. These findings support its further clinical development as a novel treatment for TROP2-expressing malignancies, including in patients previously treated with sacituzumab- or datopotamab-based regimens.

P1, N=19, Not yet recruiting, Shanghai Gynecologic Oncology Group

TROP2 promotes CRC bone metastasis by interacting with bone marrow-derived FN-integrin axis. Through its adhesive function, TROP2 may coordinate with the specialized bone niche to facilitate metastatic colonization and establish a permissive environment for stromal-tumor interactions. Targeting this axis offers a promising therapeutic strategy for managing bone metastasis in CRC and potentially other TROP2-overexpressing malignancies.

No statistically significant differences in ORR were detected according to prior CDK4/6 inhibitor exposure, number of prior treatment lines, or study design; however, these findings should be interpreted cautiously given the limited number of studies and substantial heterogeneity. Within a continuously evolving treatment landscape, further prospective studies are warranted to better define the optimal positioning of SG.

P2, N=37, Active, not recruiting, Chinese University of Hong Kong | Recruiting --> Active, not recruiting

P2, N=120, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Jun 2028 --> Jun 2030 | Trial primary completion date: Jun 2026 --> Jun 2028

P1/2, N=1132, Recruiting, Hoffmann-La Roche | N=792 --> 1132

Antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) offer new and potent options for curing for curing hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-low advanced breast cancer; however, comparisons in terms of their relative effectiveness and safety concerns are lacking. Compared with other ADC drugs, T-DXd showed relatively better treatment characteristics, better PFS benefit, and relatively low incidence of serious AEs (SAEs). Combined with RCTs and real-world data, T-DXd has potential advantages in this population.

ADCs against TROP2 (Sacituzumab govitecan) or HER2 (T-DXd) have demonstrated efficacy in metastatic breast cancer, yet paradoxically, outside of HER2-amplified breast cancers, expression levels of these breast cancer-enriched epitopes in tumor biopsies have not been strongly correlated with clinical response. Thus, while CTC burden is correlated with response to these ADCs, the level of TROP2 or HER2 expression is poorly predictive. These findings point to sensitivity to the drug payload as a potential driver of clinical response to currently approved ADCs in breast cancer.

With the expanding use of trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), and datopotamab deruxtecan (Dato-DXd) across HER2-positive, HER2-low, and hormone-receptor-positive disease, management of treatment-related toxicities has become a critical determinant of outcomes. Integrating these findings, we propose practical algorithms for managing pulmonary, gastrointestinal, hematologic, ocular, and mucosal adverse events. This review consolidates evidence into a clinician-oriented reference for ADC toxicity management, emphasizing multidisciplinary coordination, early recognition, and system-specific mitigation strategies to enhance treatment safety and adherence.